4.6 Article

p53β: a new prognostic marker for patients with clear-cell renal cell carcinoma from 5.3 years of median follow-up

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CARCINOGENESIS
卷 39, 期 3, 页码 368-374

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OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgy001

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  1. Foundation for Outstanding Young Scientist in Shandong Province [BS2011SW039]
  2. National Natural Science Foundation of China [81300629, 81572534]

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We previously reported six different p53 isoforms in renal cell carcinoma (RCC). In the present study, influences of p53 beta on recurrence-free survival (RFS) and overall survival (OS) were evaluated. Patients diagnosed with RCC in our center were into this study. mRNA expressions of p53 isoforms (p53 alpha, p53 beta, p53 gamma) in tumors were determined by RT-PCR and real-time PCR. Functional yeast-based assay was performed to analyze p53 mutational status. p53 beta transfected 786-O and CAKi-1 cells were cultured to examine expressions of B-cell lymphoma 2-associated X protein (bax) and caspase-3, and ratios of apoptosis. After surgeries, all patients were followed up at programmed intervals. 266 patients were analyzed in this study. Median follow-up time was 5.3 years. RT-PCR (r = -0.72, P = 0.016) and real-time PCR (r = -0.65, P = 0.033) both showed only p53 beta expressed higher level in lower tumor stage versus higher stage. p53 wild-type and p53 mutation had comparable RFS (P = 0.361) and OS (P = 0.218), respectively. Kaplan-Meier analysis showed high p53 beta expression was associated with significantly improved RFS and OS, regardless of p53 mutational status. High p53 beta expression indicated better RFS [hazard ratio (HR) 2.599, 95% confidence interval (CI) 1.472-4.551, P = 0.038] and OS (HR 2.604, 95% CI 1.453-4.824, P = 0.031). p53 beta transfected 786-O and CAKi-1 cells expressed significantly higher level of bax and caspase-3, and had higher ratios of apoptosis than untransfected cells. Taken together, higher level of p53 beta predict better prognosis in patients with RCC through enhancing apoptosis in tumors.

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